Adhesive-coated sheet material incorporating anti-bacterial substances

ABSTRACT

Adhesive-coated liquid-impervious moisture-vapor-permeable thin polymer sheet suitable as a wound covering has an antibacterial, preferably a solid such as silver sulphadiazine, disseminated throughout the adhesive layer, usually in amounts up to 15 wt. %, to provide uniform antibacterial properties over the wound and surrounding skin areas.

This invention relates to sheet material used for medical purposes.

More especially this invention relates to polymeric sheet material ofhigh moisture vapour permeability having upon one surface a layer ofadhesive material which does not destroy the said permeability.

Such material is already known per se and is described in British Pat.No. 1 280 631 in general terms. It is available, for example, under theRegistered Trade Mark "Op-Site". It is used as a surgical and dressingmaterial to cover wounds (including burns) and surgical sites. In thismanner it is effective to keep bacteria from the wound, and to preventscab formation and inhibit scarring since the layer, while permeable tomoisture vapour, obviously slows down the drying time of the wound.

Such material is commonly made of polyurethane sheet, e.g. Goodrichpolyether polyurethane sold under the Trade Name "Estane", which can beup to three thousandths of an inch (75 microns) in thickness but iscommonly less than 45 microns e.g. about 30 microns. It is coated on onesurface with a continuous or discontinuous layer of suitable adhesive toapproximately the same thickness. By continuous we mean that theadhesive covers the whole surface without any gaps or blank spaces; bydiscontinuous we mean that there is a microporous adhesive, or a patternof lines or dots of adhesive, the pattern covering the whole surfaceuniformly but of course leaving occasional gaps between units ofadhesive. Both of these expedients are well known in the coating art,but continuous adhesive is preferred in this context to plug any smallpinholes in the sheet.

Although a sheet of material as described is effective in keeping fromthe wound or surgical site airborne bacteria, there remains the problemof any bacteria which happen to be present in the site or, morecommonly, upon the surrounding skin. In the enclosed conditions providedby such a sheet, such bacteria can multiply unduly and lead to aninfection problem.

It has been proposed to overcome this by liberal application ofbacteriocidal or bacteriostatic cream or like formulation over andaround the wound or surgical site. There are, however, disadvantages inthis procedure since the film, if subsequently applied over this moistcream base layer, can corrugate with movement of the body and generallydoes not adhere.

The present invention is based upon the realisation that abacteriostatic or bacteriocidal material can be incorporated into theadhesive layer of the sheet.

The invention accordingly consists in an adhesive-coated sheet materialwhich is liquid-impervious but has a high moisture-vapour permeabilitywhereby it is suitable as a wound or burn dressing, or surgical drape orlike wound-covering material, wherein the adhesive coating hasdisseminated throughout its mass an amount of an antibacterial materialsufficient to kill bacteria in the wound and surrounding covered skinarea.

As well as preserving adhesion and avoiding corrugation, this inventionhas two advantages. Firstly, the antibacterial substance beingdisseminated throughout the adhesive is present in uniform known amountper unit area both over the wound and over its surroundings. Secondly,no additional substrate is needed so that the sheet can be accuratelyemplaced on the skin. As already stated, it then lies flat on the skinwith consequent uniform water vapour transmission and bacterial barrierproperties. Also avoidance of corrugations allows retention ofprotective and healing wound exudate over burns.

The antibacterial materials could be bacteriostatic but are usuallybactericidal in nature. Various types of such materials could be usedeg:

(i) metal salts, or like compounds with antibacterial metal ions, e.g.copper, mercury or silver, and optionally with additional nonmetallicions of antibacterial properties.

(ii) typical antibiotics e.g. neomycin, soframycin, bacitracin,polymycin.

(iii) antibacterials such as chlorhexidine and its salts

(iv) quaternary ammonium compounds e.g. cetrimide, domiphen bromide,polymeric quaternaries, and

(v) iodophors such as povidone iodine.

The above compounds are in some instances solid materials, and in someinstances liquids: moreover, some can be presented in either form. It ismuch preferred, however, for solid and finely divided materials to beused.

Again, some of the finely divided solids rely on the presence andactivity of a relatively small atom or group such as a metal, othersrely on the presence and activity of a large ionized group, and othersagain on both. Those utilizing metal ions are most preferable,especially if in combination with another active group.

Most preferred of all for incorporation into the adhesive layer issilver sulphadiazine in finely divided form.

We have found that up to 25% i.e., 1% to 25% (by weight of adhesive) ofthe antibacterial, but more preferably up to 15% by weight can be used.The lower limit can be as low as 1% but is preferably 5% for effectiveantibacterial properties 5% to 5% is a suitable range.

If a dispersed material, such as silver sulphadiazine, is used it isgenerally a so called "micronised" material. In this the state ofsubdivision of the material is generally speaking such that 99% of theparticles are less than 20 microns in diameter and 90% less than 10microns. In practice the majority of the particles are less, and usuallyconsiderably less, than 5 microns in diameter and are usually completelyembedded in the adhesive layer. It is of no disadvantage however if someof the particles project from the adhesive layer since theirantibacterial activity is thereby immediately exerted. Indeed, someparticles might even bridge the layer from the outside adhesive surfaceto the polymer.

Although the invention as claimed is not to be construed as relying uponany hypothesis as to the mode of action, it can reasonably be inferredthat some solid particles are embedded well within the adhesive coatingthickness while others lie near the surface from which (depending on therelative properties of the adhesive and particles), they may protrude assuch or may be separated by a thin film of polymer. Thus, when thewound-covering is applied the immediately available surface particlesact forthwith to yield up their antibacterial content, whether or notthis is in the form of large ions or small ions, but after this theprocess is conceivably controlled by ionic diffusion through theadhesive thickness in which the smaller (e.g. metal) ions are moreeffective. In addition to this, over the mobile and wet wound itself, asdistinct from the surrounding more or less stationary and static skin,conditions may be to plasticize the adhesive layer and improve migrationof the antibacterial.

Whatever the reasoning the results are not predictable in detail, someantibacterials giving less effective results than might have beenexpected and others more effective results. In particular silversulphadiazine, notwithstanding its dissemination throughout awater-insoluble adhesive and its own innate water-insolubility givesinteresting and valuable results.

As before, the polymer sheet is preferably polyurethane and can be up to75 microns in thickness. More preferably it is 40 microns or less, forexample about 30 microns.

The adhesive is usually a polyvinyl ether but is possibly an acrylicadhesive and can also be up to 75 microns in thickness, but ispreferably less than 40 microns and usually about 30 microns inthickness.

In the field of medical products high specifications of uniformity,safety, non-toxicity and comfort must be met. The preferred products ofthe invention have been assessed in various respects, as itemized below,and found to be improved or not significantly deteriorated.

Thus, for example, it was found that even keeping the total adhesiveweight (gms/sq.meter) more or less uniform at different silversulphadiazine loadings the resultant changes in thickness and uniformitywere still within acceptable limits. Also, even after ethylene oxidesterilization, and optionally forced aging, or gamma-irradiation thepermeability of these dressings at different percentage loadings ofsilver sulphadiazine to water vapours, oxygen or carbon dioxide was notsignificantly changed. Similar results were obtained for tensile andelastic tests, that is to say, no significant differences. Adhesiveproperties differed slightly after gamma-irradiation for sterilising,but this is an effect on the adhesive (rather than due to theincorporation of silver sulphadiazine) and in any case is not in respectof the adhesion to moist skin.

One area of slight difference is in light-fastness. The sterilizationprocedures mentioned above can cause some slight discoloration, but notenough to render the film opaque so that the wound cannot be observed.This is probably a consequence of the use of a silver salt, although thefilm itself is known to discolour upon exposure to sunlight.Nonetheless, rapid stock turnover minimises this problem.

The invention will be further described with reference to the followingExamples.

EXAMPLE 1

The adhesive formulation was made up as follows, to a solid content of30%:

    ______________________________________                                                         g                                                            ______________________________________                                        Bakelite EHBM      134.5                                                      Bakelite EHBC      58.8                                                       Kelrez 42463       24.0                                                       Nonox WSL (antioxidant)                                                                          1.4                                                        Toluene            53.8                                                       SBP 2              96.9                                                       (standard Petroleum spirit)                                                   ______________________________________                                    

Bakelite Resin EHBM is a poly (vinyl ethyl ether) high viscosity resinhaving 25% non-volatiles in hexane, a reduced viscosity at 20° C. of4.0±0.5; a plasticity of 1.6 to 2.0 m.m; a flash point <20° F.; aspecific gravity of 0.7299 and a weight per gallon of 6.07 lbs.

Bakelite Resin EDBC is a poly (vinyl ethyl ether) low viscosity resinhaving 98% non-volatiles; a reduced viscosity of 20° C. of 0.3±0.1; anda specific gravity at 20° C. of 0.973.

Kelrex ZR142 is a zinc resinate formed by the interaction of zinc oxideswith the resin acids in partially dimerised Colophony, contains 9.6%zinc and has a melting point of 160° to 165° C.

Into the above formulation was incorporated 1% of silver sulphadiazine,which is, on a dry basis, 590 milligrams per 100 grams of the mass.

The resulting adhesive was knife-spread on to the 25-micron polyurethanefilm and was thereafter air-dried for two hours at ambient temperature.A disc of the adhesive-coated film incorporating the silversulphadiazine, 17 millimeters in diameter was cut and placed adhesiveside down on to neomycin assay agar plates preseeded with eitherBacillus subtilis or Pseudomonas aeruginosa. The plates were left atroom temperature for approximately half an hour and then incubatedovernight at the optimum temperature for growth. After incubation thezones of inhibited growth around the discs were measured. In each casethere was a halo of destruction of the bacteria around the edges of thedisc.

EXAMPLE 2

The above experiment was repeated except that 10% by weight of thesilver sulphadiazine was incorporated into the adhesive. The results,using the same-sized discs as in Example 1, were (for Bacillus subtilis)a 34-millimeter diameter zone of inhibition and (for Pseudomonasaeruginosa) a 28.9 millimeter diameter zone, in each case including thediameter of the disc.

EXAMPLE 3

A comparative test was carried out on surgical drape samples containingzero (control) 5% and 10% by weight (nominal) of silver sulphadiazine(SSD) in the adhesive, as follows:

    ______________________________________                                        83 Control    Nominal 5% SSD                                                                             Nominal 10% SSD                                    Pts. by wt.   Pts. by wt.  Pts. by wt.                                        ______________________________________                                        Bakelite                                                                              36.4      36.4         36.4                                           EHBM                                                                          Bakelite                                                                              15.9      15.9         15.9                                           EHBC                                                                          Kelrez  6.5       6.5          6.5                                            42463                                                                         Nonox   0.4       0.4          0.4                                            WSL                                                                           Toluene 14.6      14.6         14.6                                           SBP 2   26.2      26.2         26.2                                           S.S.D.  NIL       1.5          3.0                                            ______________________________________                                    

The solids content of the adhesive prior to spending is 30%. Thus, eachsample contained 100 g of solution (30 gms solids) plus the additionalSSD content. Therefore, the nominal 5% sample contained 4.8 wt.% SSD andthe nominal 10% sample contained 9.1 wt.% SSD. 1 Kg weights of masseswere made by the following procedure:

1. Toluene and S.S.D. powder were mixed at high speed for 5 minutes.

2. The speed was reduced to slow and Kelrez and Nonox added over 10minutes.

3. Mixing continued for 20 minutes.

4. Addition of EHBC resin carried over 10 minutes.

5. Addition of EHBM resin carried over 20 minutes.

6. SBP2 was added.

7. Mixing continued for further 50 minutes.

Total mixing time=2 hrs.

A 23 micron layer of adhesive was spread onto a 25 micron polyurethanefilm using a conventional adhesive spreading tunnel and the film cutinto surgical drapes. The adhesive weight was approximately 30 grams persquare meter.

Various physical and chemical tests were conducted in the samples but nosignificant differences in physical properties (e.g. gas and moisturepermeability, adhesion, and tensile strength) were noted. The samplesincorporating SSD also withstood ageing and sterilization treatments toa similar extent to the control sample.

The samples were then subject to microbiological evaluation with respectto a variety of bacterial challenges.

Samples of drapes, after ethylene oxide sterilisation, were tested bythe zone diffusion technique. Discs of Opsite were placed with theadhesive down on neomycin assay agar plates, preseeding with challengeorganisms. After incubation, the plates were examined and zones ofinhibited growth around the samples measured.

The diameter of the discs was 10 mm, and the diameter of the inhibitedzones around (and including) the discs was as follows:

    ______________________________________                                        Content of                                                                    S.S.D. %       Zone diameter (mm) including Opsite                            Test organism  0          5        10                                         ______________________________________                                        Staph. aureus  11.9       13       15.2                                       Ps. aeuruginosa                                                                              no zone    I        13.8                                       Eschericia coli                                                                              no zone    13       14                                         Candida albicans                                                                             no zone    I        I                                          Bacillus subtilis                                                                            no zone    I        15.7                                       ______________________________________                                         I No Zone around dressing but growth inhibited beneath samples.          

I claim:
 1. An adhesive-coated sheet material which is liquid-imperviousbut has a high moisture vapor permeability whereby it is suitable as awound or burn dressing, surgical drape, or like wound-covering material,which comprises a suitable sheet having coated on one surface thereof acontinuous layer of an adhesive which has incorporated thereinto in auniform known amount per unit area an amount of an antibacterial silversalt sufficient to kill bacteria in the wound and surrounding coveredskin area.
 2. A sheet material according to claim 1 wherein the silversalt is in finely divided solid form.
 3. A sheet material according toclaim 1 in which the silver salt is silver sulphadiazine.
 4. A sheetmaterial according to claim 1 wherein the amount of silver salt is from1 to 25% by weight based on the weight of the adhesive.
 5. A sheetmaterial according to claim 4 wherein the amount is from 5 to 15% byweight.
 6. A sheet material according to claim 1 wherein the silver saltis particulate and the majority of the particles are less than fivemicrons in diameter.
 7. A sheet material according to claim 1 whereinthe sheet is polyurethane up to 75 microns in thickness.
 8. A sheetmaterial according to claim 1 in which the adhesive is a layer of apolyvinyl ether up to 75 microns in thickness.
 9. A sheet materialaccording to claim 7 or 8 in which each layer is up to 30 microns inthickness.
 10. A sheet material according to claim 1 which additionallycomprises a peelable release layer on the adhesive face, to be removedprior to use.
 11. A sheet material according to claim 1, in which theadhesive layer is acrylic adhesive up to 75 microns in thickness.
 12. Asheet material according to claim 1, in which adhesive layer is acrylicadhesive up to 40 microns in thickness.
 13. A sheet material accordingto claim 1, in which the adhesive layer is acrylic adhesive up to about30 microns in thickness.
 14. A sheet material according to claim 8,wherein the layer of a polyvinyl ether is up to 30 microns in thickness.15. A sheet material according to claim 7, in which the polyurethanesheet is 40 microns or less in thickness.
 16. A sheet material accordingto claim 7, in which the polyurethane sheet is about 30 microns inthickness.
 17. A sheet material according to claim 8 wherein the layerof a polyvinyl ether is less than 40 microns in thickness.
 18. A sheetmaterial according to claim 1 wherein the sheet material is a 25 micronpolyurethane film and the adhesive consists essentially of a polyvinylethyl ether high viscosity resin having 25% non-volatiles in hexane, areduced viscosity at 20° C. of 4.0±0.5; a plasticity of 1.6 to 2.0 m.m;a flash point less than 20° F.; a specific gravity of 0.7299 and aweight per gallon of 6.07 lbs.; a polyvinyl ethyl ether low viscosityresin having 98% non-volatiles; a reduced viscosity of 20° C. of0.3±0.1; and a specific gravity at 20° C. of 0.973; a zinc resinateformed by the interaction of zinc oxides with the resin acids in apartially dimerised Colophony, containing 9.6% zinc and having a meltingpoint of 160° to 165° C., an antioxidant, Toluene, and standardpetroleum spirits into which was incorporated 1% by weight of silversulphadiazine which is, on a dry basis, 590 milligrams per 100 grams ofmass.
 19. A sheet material according to claim 1 wherein the sheetmaterial is a 25 micron polyurethane film and the adhesive consistsessentially of a polyvinyl ethyl ether high viscosity resin having 25%non-volatiles in hexane, a reduced viscosity at 20° C. of 2.0±0.5; aplasticity of 1.6 to 2.0 m.m; a flash point less than 20° F.; a specificgravity of 0.7299 and a weight per gallon of 6.07 lbs.; a polyvinylethyl ether low viscosity resin having 98% non-volatiles; a reducedviscosity of 20° C. of 0.3±0.1; and a specific gravity at 20° C. of0.973; a zinc resinate formed by the interaction of zinc oxides with theresin acids in a partially dimerised Colophony, containing 9.6% zinc andhaving a melting point of 160° to 165° C., an antioxidant, Toluene, andstandard petroleum spirits into which was incorporated 10% by weight ofsilver sulphadiazine which is, on a dry basis, 590 milligrams per 100grams of mass.
 20. A sheet material according to claim 1 wherein thesilver salt is in micronized form.